Unsupervised multi-modal data analysis reveals features underlying spatial heterogeneity and immune responses in non-small cell lung cancer: results

Heatmaps of RNA-sequencing data

Jia Sharma

Heatmap depicting the RNA data of Jia and Sharma

TCGA

Heatmap depicting the RNA data of TCGA

Heatmaps of Processed Features

Jia

Heatmaps depicting the Feature data of Jia dataset

Sharma

Heatmaps depicting the Feature data of Sharma dataset

LUAD

Heatmaps depicting the Feature data of LUAD dataset

LUSC

Heatmaps depicting the Feature data of LUSC dataset

CRC

Heatmaps depicting the Feature data of CRC dataset

SKCM

Heatmaps depicting the Feature data of SKCM dataset

PBMC

Heatmaps depicting the Feature data of PBMC dataset

MOFA results

Results of the Jia and Sharma dataset analysis

Jia

## $Jia
##   RNAseq 
## 68.23396 
## 
## $Jia
##            RNAseq
## Factor1 26.109267
## Factor2 15.140792
## Factor3  9.273429
## Factor4  6.395170
## Factor5  4.921713
## Factor6  3.645070
## Factor7  2.840035

## $Jia
## Immune cells quantification              Pathway scores 
##                    31.88450                    75.50269 
##       Transcription factors 
##                    81.80199 
## 
## $Jia
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  9.04474250      25.619542             40.579562
## Factor2                 16.46881862      13.041630              6.059506
## Factor3                  4.16318229      12.482454             14.195675
## Factor4                  0.48687257      10.815804              9.561976
## Factor5                  1.12789197       5.140326              6.429715
## Factor6                  0.61185598       5.309700              2.828404
## Factor7                  0.01614819       2.168045              3.477739

Heatmap depicting the MOFA results of Jia dataset

Sharma

## $Sharma
##   RNAseq 
## 78.48807 
## 
## $Sharma
##            RNAseq
## Factor1 31.254935
## Factor2 17.949286
## Factor3 10.726381
## Factor4  9.399917
## Factor5  4.249152
## Factor6  3.876981
## Factor7  2.002550

## $Sharma
## Immune cells quantification              Pathway scores 
##                    64.05056                    85.57834 
##       Transcription factors 
##                    88.57098 
## 
## $Sharma
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  6.22868202      45.146261             49.987368
## Factor2                 53.39957855       2.156345              4.482683
## Factor3                  4.50626823      17.422461              4.940097
## Factor4                  0.81207957       6.209092             11.575719
## Factor5                  0.21740030       4.861718             10.070898
## Factor6                  0.29306489       6.154450              5.623257
## Factor7                  0.05845285       2.340754              2.554429

Heatmap depicting the MOFA results of Sharma dataset

Jia-Sharma combined

## $Jia
##   RNAseq 
## 63.49116 
## 
## $Sharma
##   RNAseq 
## 53.91061 
## 
## $Jia
##            RNAseq
## Factor1 25.554560
## Factor2 11.992019
## Factor3  1.282114
## Factor4 10.905898
## Factor5  6.423837
## Factor6  3.041194
## Factor7  4.252318
## 
## $Sharma
##             RNAseq
## Factor1 22.7049103
## Factor2 11.1926794
## Factor3 13.4522387
## Factor4  2.9412181
## Factor5  1.0376639
## Factor6  3.5540332
## Factor7  0.9137955

## $Jia
## Immune cells quantification              Pathway scores 
##                    21.34774                    71.64954 
##       Transcription factors 
##                    78.32020 
## 
## $Sharma
## Immune cells quantification              Pathway scores 
##                    20.35690                    58.88863 
##       Transcription factors 
##                    74.50499 
## 
## $Jia
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                   9.4420220      24.238854             37.373011
## Factor2                   0.7418870       9.503687             15.918343
## Factor3                  10.7504973      12.705553              5.856245
## Factor4                   0.5690629       6.457295              8.918773
## Factor5                   0.2254012      10.236809              4.819569
## Factor6                   0.7581855       2.443406              3.351741
## Factor7                   0.1695355       3.968168              4.310816
## 
## $Sharma
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                 8.711650804     36.4894661             45.074942
## Factor2                -0.464040829      2.8603389             11.397810
## Factor3                 6.928408588      1.4788415              1.362861
## Factor4                 2.099729742      9.6558138              9.012147
## Factor5                 1.077867091      7.5636400              1.553084
## Factor6                 0.378333699      2.2220397              5.433451
## Factor7                 0.003460828      0.6104246              3.547656

Heatmap depicting the MOFA results of RNA-seq analysis of the Jia-Sharma dataset

LUAD

## $LUAD
##   RNAseq 
## 36.04769 
## 
## $LUAD
##            RNAseq
## Factor1 10.578338
## Factor2  7.755154
## Factor3  4.574471
## Factor4  4.459151
## Factor5  3.215678
## Factor6  3.186303
## Factor7  2.584139

## $LUAD
## Immune cells quantification              Pathway scores 
##                    24.20549                    40.10403 
##       Transcription factors 
##                    61.79617 
## 
## $LUAD
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                   10.551752       8.008269             22.508832
## Factor2                    1.337535       9.847336             14.387137
## Factor3                    2.920561       5.496181             12.589275
## Factor4                    6.742311       6.216552              1.840613
## Factor5                    1.266392       7.147005              6.152219
## Factor6                    1.386933       3.388691              4.318094

Heatmap depicting the MOFA results of LUAD dataset

LUSC

## $LUSC
##   RNAseq 
## 39.59177 
## 
## $LUSC
##            RNAseq
## Factor1 12.830726
## Factor2  7.306695
## Factor3  5.448373
## Factor4  4.717565
## Factor5  3.938002
## Factor6  3.281719
## Factor7  2.160142

## $LUSC
## Immune cells quantification              Pathway scores 
##                    25.91362                    54.33659 
##       Transcription factors 
##                    77.37114 
## 
## $LUSC
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  13.8213517      13.467181            32.2411668
## Factor2                   3.9561132      10.432106            15.5878992
## Factor3                   5.2129073       6.257736             5.8180351
## Factor4                   0.2552738       4.396189             8.0073593
## Factor5                   1.3935745       7.104439             2.8584741
## Factor6                   0.6314688       2.195804             5.3377074
## Factor7                   1.4115221       2.630566             0.6968012

Heatmap depicting the MOFA results of LUSC dataset

NSCLC

## $NSCLC
##   RNAseq 
## 41.78628 
## 
## $NSCLC
##            RNAseq
## Factor1 17.725410
## Factor2  7.082743
## Factor3  5.370592
## Factor4  4.021149
## Factor5  3.057802
## Factor6  2.840507
## Factor7  2.154332

## $NSCLC
## Immune cells quantification              Pathway scores 
##                    19.92243                    52.70010 
##       Transcription factors 
##                    74.02841 
## 
## $NSCLC
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  10.6849023       9.436347             24.831503
## Factor2                   0.8309582      12.608703              6.934714
## Factor3                   1.5619903       5.351272             11.795849
## Factor4                   1.7179859       3.821442              8.524851
## Factor5                   0.7268656       3.873664              4.983322
## Factor6                   1.6017107       4.304303              3.309388
## Factor7                   1.3362683       2.999443              2.449172

Heatmap depicting the MOFA results of NSCLC dataset

CRC

## $CRC
##   RNAseq 
## 40.32648 
## 
## $CRC
##            RNAseq
## Factor1 17.251105
## Factor2  9.149151
## Factor3  5.121999
## Factor4  3.429345
## Factor5  2.265343
## Factor6  1.888763
## Factor7  1.751464

## $CRC
## Immune cells quantification              Pathway scores 
##                    22.32748                    46.53928 
##       Transcription factors 
##                    66.10702 
## 
## $CRC
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  13.4793838      19.074814             31.329550
## Factor2                   2.6458338       9.873936             16.205573
## Factor3                   2.8161162       5.304654              9.593038
## Factor4                   2.2873662       4.936317              3.522675
## Factor5                   1.0840800       4.071545              2.802916
## Factor6                   0.0147043       3.278018              2.653271

Heatmap depicting the MOFA results of CRC dataset

SKCM

## $SKCM
##   RNAseq 
## 40.06379 
## 
## $SKCM
##            RNAseq
## Factor1 11.572346
## Factor2  8.838881
## Factor3  6.716767
## Factor4  4.677261
## Factor5  4.149576
## Factor6  2.745333
## Factor7  1.589064

## $SKCM
## Immune cells quantification              Pathway scores 
##                    25.48666                    57.29829 
##       Transcription factors 
##                    76.42455 
## 
## $SKCM
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                  16.0441325      19.908703             38.866783
## Factor2                   1.4521253       9.139358             13.493822
## Factor3                   1.3222194       8.842419              6.355452
## Factor4                   3.4132786       9.520523              2.666744
## Factor5                   1.5271311       2.797199              8.710657
## Factor6                   0.6765548       5.478299              3.719744
## Factor7                   0.6073407       2.133412              2.213119

Heatmap depicting the MOFA results of SKCM dataset

PBMC

## $PBMC
##   RNAseq 
## 76.49658 
## 
## $PBMC
##            RNAseq
## Factor1 63.966862
## Factor2  8.426346
## Factor3  2.597099
## Factor4  1.506278

## $PBMC
## Immune cells quantification              Pathway scores 
##                    64.53760                    69.49374 
##       Transcription factors 
##                    72.75441 
## 
## $PBMC
##         Immune cells quantification Pathway scores Transcription factors
## Factor1                5.756328e+01   5.747104e-04             10.333415
## Factor2                8.467576e-04   2.469436e+01             25.470690
## Factor3                2.633135e+00   1.634614e+01             21.055315
## Factor4                5.061628e-01   1.485045e+01              7.471381
## Factor5                3.534691e+00   1.088466e+01              2.210367
## Factor6                2.994938e-01   2.717556e+00              6.213241

Heatmap depicting the MOFA results of PBMC dataset

Venn-diagram genes

Feature analysis

Correlations between the feature-based models

Heatmap depicting the correlation of all factors of all models based on feature data. Only significant relations (p<0.001) are shown.

Heatmaps of feature-weights

Heatmap depicting the results of the feature analysis of all datasets.

RNA analysis

Correlations of all RNA-seq based factors

Heatmap depicting the correlation of all factors of all models based on RNA data. Only significant relations (p<0.001) are shown.

GSEA: GO annotation set

Heatmap depicting the results of the GSEA analysis using the GO annotation set.

GSEA: Hallmark annotation set

Heatmap depicting the results of the GSEA analysis using the Hallmark annotation set.

Immunotherapy

Response to immunotherapy: features

Correlations to immune response: Features

Response to immunotherapy: RNA

Correlations to immune response: RNA

Within-patient response Jia & Sharma

Results bootstrapping

Overview of bootstrapped mean values

Beeswarm plots showing the intra-patient variability of the highlighted features for the Jia and Sharma dataset